title: Anaphylactic responses to histamine in mice utilize both histamine receptors 1 and 2.
abstract: BACKGROUND
  Anaphylaxis is a severe, potentially life-threatening reaction that can occur in response to common triggers, including food allergens (e.g., peanut), insect stings, and several medications. Activation of mast cells and basophils to release preformed mediators, such as histamine, is thought to be an important process that underlies reactions. Histamine can exert effects through four different receptors, termed H1R-H4R. Despite clinical use of both H1R and H2R blockers in the therapy for acute allergic reactions, there is little mechanistic evidence to support the necessity for blocking H2R, a receptor best characterized for its role in stomach acid production.
  
  
  METHODS
  Here, we sought to define the necessity for histamine receptors in the pathology of anaphylaxis using H1R and H2R knockout (KO) mice, as well as a H1R/H2R double KO strain.
  
  
  RESULTS
  In response to IgE-mediated systemic anaphylaxis, the symptoms and decreases in core body temperature observed in wild-type mice were reduced but not ablated in either H1R or H2R KO. In contrast, H1R/H2R KO were significantly protected and were indistinguishable from histamine-deficient mice. Intravenous injection of histamine was sufficient to elicit these responses, and similar to IgE-mediated anaphylaxis, loss of both H1R and H2R was necessary for complete protection.
  
  
  CONCLUSIONS
  Our data demonstrate definitively that both H1R and H2R participate in the immediate systemic responses during histamine-associated pathophysiology and mechanistically support the utility of H2R-blocking therapeutics in alleviating symptoms of anaphylaxis.
authors.affiliation: Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Wechsler
authors.forename: H A
authors.initials: HA
authors.lastname: Schroeder
authors.forename: A J
authors.initials: AJ
authors.lastname: Byrne
authors.forename: K B
authors.initials: KB
authors.lastname: Chien
authors.forename: P J
authors.initials: PJ
authors.lastname: Bryce
mesh_terms: D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D004195:Disease Models, Animal; D006632:Histamine / Q000097:blood / Q000378:metabolism*; D007073:Immunoglobulin E / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000276:immunology; D011969:Receptors, Histamine H1 / Q000235:genetics / Q000378:metabolism*; D011970:Receptors, Histamine H2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D007073:Immunoglobulin E; D006632:Histamine; D010047:Ovalbumin
keywords: IgE; anaphylaxis; antihistamine; histamine